Functionality improvement of Chlorzoxazone by crystallo-co-agglomeration using multivariate analysis approach

Abstract

The aim of present work was to improve physicochemical properties of model drug Chlorzoxazone by crystallo-co-agglomeration (CCA) in the presence of different polymers and excipients. Identification of Quality Target Product Profile and Critical Quality Attributes were done using Risk assessment and Failure mode effect analysis. CCA was formulated by applying Box–Behnken design followed by principal component analysis (PCA). CCA was further studied for its topographical, micromeritic, mechanical, compressional, and dissolution properties. Prepared CCA showed improvement in flow and packability with rich drug content (90.84%). Heckel parameters indicated greater plastic deformation (K = 0.8132) and tensile strength compared to the pure drug (K = 19.256 kg/cm²). CCA showed negligible elastic recovery (0.87%) compared to the pure drug (5.708%). Dissolution of the drug was increased to 2.69-folds compared to the pure drug after 60 min. No degradation or polymorphic transformation of the drug was observed even after stability study (40 °C, 75% RH). The amount of directly compressible diluents could be minimized in tablet formulation, which was a considerable improvement in the properties of the drug for making directly compressible form. The study highlights an improvement of processing characteristics of Chlorzoxazone by CCA using an integrated approach of QbD and PCA.

Keywords:

• Chlorzoxazone
• crystallo-co-agglomeration
• principal component analysis
• failure mode effect analysis
• loading plot

Acknowledgments

The authors are grateful to Evonic Degussa Incorporation Pvt. Ltd., Mumbai, India, for providing gift samples of Eudragit. Authors are thankful to Shri K. Chudasama and Shri Sheth, ERDA, Baroda, for providing the facility of SEM analysis. Authors are highly obliged to Dr. CVS Subrahmanyam—Hyderabad, Dr. A. K. Bansal, NIPER-Mohali for providing their valuable support in this study.

Disclosure statement

The authors declared no conflict of interest.